The objective of the proposed research is to seek answers by the use of mouse chimeras to various questions regarding mammalian limb development, such as whether the limb system as a whole is specified by one or more precursor cells, whether there is regional independence (proximo-distal, preaxial-postaxial) in control of development, etc. Mouse chimeras result when two midcleavage-stage mouse embryos of different potential phenotypes are united into a single embryo. In the proposed research, one of the two embryos will be a normal embryo, the other one a mutant for one of several genes which have drastic effects on the mouse limb skeleton. It is expected that examination of the limbs of the chimeric mice resulting from such unions will reveal how the different contributing genotypes interact to affect limb development and will provide answers to the questions regarding limb development alluded to above. This research will be the first to use mouse chimeras to analyze factors affecting limb development.